This COBRE application proposes to continue The Nebraska Center for Cellular Signaling that was established to strengthen the research within UNMC and particularly the College of Dentistry. The stated objectives of the Center were 1) to expand the current focus on cellular signaling;2) to increase the research profile of Nebraska's dental schools, with the ultimate goal of being included in the top dental schools in the country in NIH funding;and, most importantly, 3) to contribute to the development of promising young faculty, so that they will become prominent members of the scientific community as evidenced by significant NIH funding, publication of important manuscripts, service on review panels and invitations to speak across the country. We have accomplished each of these goals with exceptional successful: We have created the necessary infrastructure consisting of 1) An organized Center comprised of a committed director, an outstanding External Advisory Board, and a group of highly dedicated Mentors, and 2) a program of development, designed to enhance and sustain the Center, that includes a seminar program, graduate student stipends and a seed grant program. With this in place, we have attracted highly talented and driven junior Project Leaders investigating inter-related research projects focused on a variety of aspects of cellular signaling, and covering disease states from developmental problems to cancer. As evidence of our success, we have supported 14 junior Project Leaders and have seen five of them funded through the NIH R01 mechanism, with two more expected to be funded in the next funding cycle. In addition, our junior Project Leaders have published or have in preparation 65 papers and manuscripts. Three of our Project Leaders serve on review panels at the NIH, Department of Defense and American Heart Association, and several have been invited speakers at national and international conferences. We have strong support from the institution and a plan in place to sustain the program when the COBRE funding expires. The PI and mentors involved in this project are committed to continuing a culture of mentoring within UNMC. In addition, the collaborative environment resulting from the formation of the Center has and will continue to enhance the research infrastructure within Nebraska's Dental and Medical Schools.